ORIGINAL CONTRIBUTIONS |
Cigarette Smoking and Colorectal Cancer: APC Mutations, hMLH1 Expression, and GSTM1 and GSTT1 Polymorphisms
1 Nutrition and Toxicology Research Institute Maastricht, Department of Epidemiology, Universiteit Maastricht, Maastricht, the Netherlands
2 Division of Human Nutrition, Wageningen University and Research Centre, Wageningen, the Netherlands
3 Department of Pathology, University Medical Centre St. Radboud, Nijmegen, the Netherlands
4 Nutrition and Toxicology Research Institute Maastricht, Department of Pathology, Universiteit Maastricht, Maastricht, the Netherlands
5 TNO Nutrition and Food Research, Zeist, the Netherlands
6 Research Institute Growth and Development, Department of Pathology, Universiteit Maastricht, Maastricht, the Netherlands
Correspondence to Dr. M. P. Weijenberg, Department of Epidemiology, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, the Netherlands (e-mail: mp.weijenberg{at}epid.unimaas.nl).
The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted incidence rate ratios for 1986–1993 were computed for overall colorectal cancer, tumors with and without adenomatous polyposis coli (APC) mutations, and tumors with and without human mut-L homologue 1 (hMLH1) expression, according to cigarette smoking characteristics (661 cases, 2,948 subcohort members). Case-only analyses were performed to estimate odds ratios for interaction between cigarette smoking and GSTM1 and GSTT1 genotypes. In comparison with never smokers, a high smoking frequency increased the risk of colorectal cancer (for a five-cigarette/day increment, incidence rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.03, 1.12), and this association was stronger in 371 tumors without a truncating APC mutation (IRR = 1.11, 95% CI: 1.05, 1.17). Long-term smoking was associated with lack of hMLH1 expression in 56 tumors (for a 10-year increment, IRR = 1.17, 95% CI: 1.00, 1.37). No statistically significant interactions between smoking and GSTM1 or GSTT1 genotype were observed. These results indicate that cigarette smoking is associated with risk of colorectal cancer, and this association may depend on molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status.
adenomatous polyposis coli; colorectal neoplasms; glutathione transferase; neoplasm proteins; polymorphism, genetic; smoking
Abbreviations: APC, adenomatous polyposis coli; CI, confidence interval; GSTM1, glutathione S-transferase M1; GSTT1, glutathione S-transferase T1; hMLH1, human mut-L homologue 1; IRR, incidence rate ratio; PALGA, Pathologisch Anatomisch Landelijk Geautomatiseerd Archief; PCR, polymerase chain reaction
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